Packaging solutions

ABSTRACT

The present invention is directed to new and improved packaging systems for storing ophthalmic devices such as contact lenses and to methods for packaging such ophthalmic devices with aqueous packaging solutions to improve the comfort of the lens during wear. In particular, the present invention is directed to a packaging system for storing an ophthalmic device in an aqueous packaging solution comprising an anionic polymer and a non-ionic polyol. Such solutions can be retained on the surface of an unused lens for extended periods of time, resulting in surface modification that persists in the eye, which may provide significant improvement in the wetting properties of fresh contact lenses used for the first time and, moreover, even several hours after lens insertion, preventing dryness and improving lubricity.

BACKGROUND OF THE INVENTION

1. Technical Field

The present invention generally relates to packaging solutions forophthalmic devices such as contact lenses.

2. Description of Related Art

Blister-packs and glass vials are typically used to individually packageeach soft contact lens for sale to a customer. Saline or deionized wateris commonly used to store the lens in the blister-packs, as mentioned invarious patents related to the packaging or manufacturing of contactlenses. Because lens material may tend to stick to itself and to thelens package, packaging solutions for blister-packs have sometimes beenformulated to reduce or eliminate lens folding and sticking. For thisreason, poly(vinyl alcohol) (PVA) has been used in contact lenspackaging solutions.

It has been stated that if a lens is thoroughly cleaned beforeinsertion, lacrimal fluid can adequately wet the lens. Furthermore, thedifficulties of adding a surfactant to a packaging solution, includingthe possibility of lowering shelf-life and/or adverse reactions duringheat sterilization, have further limited the use of surfactants in apackaging solution for the purpose of providing any possible or marginaleffect on lens comfort. It is only after a lens has been worn, whenproteins or other deposits have formed on the surface of the lens, thatsurfactants have been used in standard lens-care solutions.

It is highly desirable that contact lens be as comfortable as possiblefor wearers. Manufacturers of contact lenses are continually working toimprove the comfort of the lenses. Nevertheless, many people who wearcontact lenses still experience dryness or eye irritation throughout theday and particularly towards the end of the day. An insufficientlywetted lens at any point in time will cause significant discomfort tothe lens wearer. Although wetting drops can be used as needed toalleviate such discomfort, it would certainly be desirable if suchdiscomfort did not arise in the first place.

U.S. Pat. No. 5,882,687 discloses a package containing a contact lenssuitable for immediate use which comprises (a) a solution comprising asoluble polyanionic component and having a viscosity of less than 50 cpsat 25° C., an osmolality of at least about 200 mOsm/kg and a pH in therange of about 6 to about 9; (b) at least one contact lens, and (c) acontainer for holding the solution and contact lens sufficient topreserve the sterility of the solution and contact lens, wherein thesolution contains no additional disinfectant component. However, apolyanion such as carboxymethylcellulose alone can possess a shape of asphere or random coil and has a Mark-Houwink Constant (α) of 0 when inthe shape of a sphere and 0.5 to 0.8 when in the shape of a random coil.This type of polyanion may not coat uniformly a surface of a contactlens, resulting in the lens being relatively uncomfortable during use.

Accordingly, it would be desirable to provide an improved packagingsystem for ophthalmic devices such as an ophthalmic lens that the lenswould be comfortable to wear in actual use and allow for extended wearof the lens without irritation or other adverse effects to the cornea.

SUMMARY OF THE INVENTION

In accordance with one embodiment of the present invention, a method ofpreparing a package comprising a storable, sterile ophthalmic device isprovided comprising:

(a) immersing an ophthalmic device in an aqueous packaging solutioncomprising an anionic polymer and a non-ionic polyol, wherein theaqueous packaging solution has an osmolality of at least about 200mOsm/kg and a pH in the range of about 6 to about 9;

(b) packaging the solution and the device in a manner preventingcontamination of the device by microorganisms; and

(c) sterilizing the packaged solution and device.

In accordance with a second embodiment of the present invention, amethod for packaging and storing a contact lens is provided comprising,prior to delivery of the contact lens to the customer-wearer, immersingthe contact lens in an aqueous packaging solution inside a package andheat sterilizing the solution, wherein the aqueous packaging solutioncomprises an anionic polymer and a non-ionic polyol, wherein the aqueouspackaging solution has an osmolality of at least about 200 mOsm/kg and apH of about 6 to about 9.

In accordance with a third embodiment of the present invention, apackaging system for the storage of an ophthalmic device is providedcomprising a sealed container containing one or more unused ophthalmicdevices immersed in an aqueous packaging solution comprising an anionicpolymer and a non-ionic polyol, wherein the aqueous packaging solutionhas an osmolality of at least about 200 mOsm/kg, a pH of about 6 toabout 9 and is heat sterilized.

In accordance with a fourth embodiment of the present invention, apackaging system for the storage of an ophthalmic device is providedcomprising:

(a) an aqueous packaging solution comprising an anionic polymer and anon-ionic polyol, wherein the aqueous packaging solution has anosmolality of at least about 200 mOsm/kg and a pH in the range of about6 to about 9;

(b) at least one ophthalmic device; and

(c) a container for holding the solution and ophthalmic devicesufficient to preserve the sterility of the solution and ophthalmicdevice, wherein the solution does not contain an effective disinfectingamount of a disinfecting agent.

By combining a non-ionic polyol with an anionic polymer such as ananionic carboxymethylcellulose to form an aqueous packaging solution, amore uniform coating of the anionic polymer may be obtained. It isbelieved that the Mark-Houwink Constant (α) of the anionic polymerincreases to a level resulting in a coating that is more uniform overthe lens, and hydrogen bonding of the anionic polymer is more effective.Thus, the lens will be more comfortable to wear in actual use and mayallow for the extended wear of the lens without irritation or otheradverse effects to the cornea.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention provides a packaging system for the storage ofophthalmic devices intended for direct contact with body tissue or bodyfluid. As used herein, the term “ophthalmic device” refers to devicesthat reside in or on the eye. These lenses can provide opticalcorrection, wound care, drug delivery, diagnostic functionality orcosmetic enhancement or effect or a combination of these properties.Representative examples of such devices include, but are not limited to,soft contact lenses, e.g., a soft, hydrogel lens; soft, non-hydrogellens and the like, hard contact lenses, e.g., a hard, gas permeable lensmaterial and the like, intraocular lenses, overlay lenses, ocularinserts, optical inserts and the like. As is understood by one skilledin the art, a lens is considered to be “soft” if it can be folded backupon itself without breaking. Any material known to produce anophthalmic device including a contact lens can be used herein. It isparticularly useful to employ biocompatible materials herein includingboth soft and rigid materials commonly used for ophthalmic lenses,including contact lenses. The preferred substrates are hydrogelmaterials, including silicone hydrogel materials and non-siliconehydrogel materials.

A wide variety of materials can be used herein. Hydrogels in general area well-known class of materials that comprise hydrated, crosslinkedpolymeric systems containing water in an equilibrium state. Hydrogelcontact lens materials are made from at least one hydrophilic monomer,such as 2-hydroxethyl methacrylate (HEMA), N-vinylpyrrolidone (NVP) orN,N-dimethylacrylamide (DMA). Hydrogels generally have a water contentgreater than about 15 weight percent and more commonly between about 20to about 80 weight percent.

One class of hydrogels is silicone hydrogels. These materials areusually prepared by polymerizing a mixture containing at least onesilicone-containing monomer and at least one hydrophilic monomer.Typically, either the silicone-containing monomer or the hydrophilicmonomer functions as a crosslinking agent (a crosslinker being definedas a monomer having multiple polymerizable functionalities) or aseparate crosslinker may be employed. Applicable silicone-containingmonomeric units for use in the formation of silicone hydrogels are wellknown in the art and numerous examples are provided in U.S. Pat. Nos.4,136,250; 4,153,641; 4,740,533; 5,034,461; 5,070,215; 5,260,000;5,310,779; and 5,358,995.

Representative examples of applicable silicon-containing monomeric unitsinclude bulky siloxanyl monomers represented by the structure of FormulaI:

wherein X denotes —O— or —NR—; each R¹ independently denotes hydrogen ormethyl; each R² independently denotes a lower alkyl radical, phenylradical or a group represented by

wherein each R^(2′) independently denotes a lower alkyl or phenylradical; and h is 1 to 10.

Examples of bulky monomers are3-methacryloyloxypropyltris(trimethyl-siloxy)silane ortris(trimethylsiloxy)silylpropyl methacrylate, sometimes referred to asTRIS and tris(trimethylsiloxy)silylpropyl vinyl carbamate, sometimesreferred to as TRIS-VC and the like.

Such bulky monomers may be copolymerized with a silicone macromonomer,such as a poly(organosiloxane) capped with an unsaturated group at twoor more ends of the molecule. U.S. Pat. No. 4,153,641 discloses, forexample, various unsaturated groups such as acryloyloxy ormethacryloyloxy groups.

Another class of representative silicone-containing monomers includes,but is not limited to, silicone-containing vinyl carbonate or vinylcarbamate monomers such as, for example,1,3-bis[4-vinyloxycarbonyloxy)but-1-yl]tetramethyl-disiloxane;3-(trimethylsilyl)propyl vinyl carbonate;3-(vinyloxycarbonylthio)propyl-[tris(trimethylsiloxy)silane];3-[tris(trimethylsiloxy)silyl]propyl vinyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl allyl carbamate;3-[tris(trimethylsiloxy)silyl]propyl vinyl carbonate;t-butyldimethylsiloxyethyl vinyl carbonate; trimethylsilylethyl vinylcarbonate; trimethylsilylmethyl vinyl carbonate and the like andmixtures thereof.

Another class of silicon-containing monomers includespolyurethane-polysiloxane macromonomers (also sometimes referred to asprepolymers), which may have hard-soft-hard blocks like traditionalurethane elastomers. They may be end-capped with a hydrophilic monomersuch as 2-hydroxyethyl methacrylate (HEMA). Examples of such siliconeurethanes are disclosed in a variety or publications, including PCTPublished Application No. WO 96/31792 discloses examples of suchmonomers, which disclosure is hereby incorporated by reference in itsentirety. Representative examples of silicone urethane monomers arerepresented by Formulae II and III:

E(*D*A*D*G)_(a)*D*A*D*E′; or  (II)

E(*D*G*D*A)_(a)*D*A*D*E′; or  (III)

wherein:

D independently denotes an alkyl diradical, an alkyl cycloalkyldiradical, a cycloalkyl diradical, an aryl diradical or an alkylaryldiradical having 6 to about 30 carbon atoms;

G independently denotes an alkyl diradical, a cycloalkyl diradical, analkyl cycloalkyl diradical, an aryl diradical or an alkylaryl diradicalhaving 1 to about 40 carbon atoms and which may contain ether, thio oramine linkages in the main chain;

* denotes a urethane or ureido linkage;

a is at least 1;

A independently denotes a divalent polymeric radical of Formula IV:

wherein each R^(s) independently denotes an alkyl or fluoro-substitutedalkyl group having 1 to about 10 carbon atoms which may contain etherlinkages between the carbon atoms; m′ is at least 1; and p is a numberthat provides a moiety weight of about 400 to about 10,000;

each of E and E′ independently denotes a polymerizable unsaturatedorganic radical represented by Formula V:

wherein: R³ is hydrogen or methyl;

R⁴ is hydrogen, an alkyl radical having 1 to 6 carbon atoms, or a—O—Y—R⁶ radical wherein Y is —O—, —S— or —NH—; R⁵ is a divalent alkyleneradical having 1 to about 10 carbon atoms; R⁶ is a alkyl radical having1 to about 12 carbon atoms; X denotes O— or —OCO—; Z denotes —O— or—NH—; Ar denotes an aromatic radical having about 6 to about 30 carbonatoms;

w is 0 to 6; x is 0 or 1; y is 0 or 1; and z is 0 or 1.

A preferred silicone-containing urethane monomer is represented by

wherein m is at least 1 and is preferably 3 or 4, a is at least 1 andpreferably is 1, p is a number which provides a moiety weight of about400 to about 10,000 and is preferably at least about 30, R⁷ is adiradical of a diisocyanate after removal of the isocyanate group, suchas the diradical of isophorone diisocyanate, and each E″ is a grouprepresented by:

In another embodiment of the present invention, a silicone hydrogelmaterial comprises (in bulk, that is, in the monomer mixture that iscopolymerized) about to about 50 percent, and preferably about 10 toabout 25, by weight of one or more silicone macromonomers, about 5 toabout 75 percent, and preferably about 30 to about 60 percent, by weightof one or more polysiloxanylalkyl (meth)acrylic monomers, and about 10to about 50 percent, and preferably about 20 to about 40 percent, byweight of a hydrophilic monomer. In general, the silicone macromonomeris a poly(organosiloxane) capped with an unsaturated group at two ormore ends of the molecule. In addition to the end groups in the abovestructural formulas, U.S. Pat. No. 4,153,641 discloses additionalunsaturated groups, including acryloyloxy or methacryloyloxy groups.Fumarate-containing materials such as those disclosed in U.S. Pat. Nos.5,310,779; 5,449,729 and 5,512,205 are also useful substrates inaccordance with the invention. Preferably, the silane macromonomer is asilicon-containing vinyl carbonate or vinyl carbamate or apolyurethane-polysiloxane having one or more hard-soft-hard blocks andend-capped with a hydrophilic monomer.

Suitable hydrophilic monomers include amides such asN,N-dimethylacrylamide and N,N-dimethylmethacrylamide, cyclic lactamssuch as N-vinyl-2-pyrrolidone and poly(alkene glycols) functionalizedwith polymerizable groups. Examples of useful functionalized poly(alkeneglycols) include poly(diethylene glycols) of varying chain lengthcontaining monomethacrylate or dimethacrylate end caps. In a preferredembodiment, the poly(alkene glycol) polymer contains at least two alkeneglycol monomeric units. Still further examples are the hydrophilic vinylcarbonate or vinyl carbamate monomers disclosed in U.S. Pat. No.5,070,215, and the hydrophilic oxazolone monomers disclosed in U.S. Pat.No. 4,910,277. Other suitable hydrophilic monomers will be apparent toone skilled in the art.

In one embodiment, the lens can be a Group II and Group IV lens having awater content greater than about 50% by weight, and preferably about 55%to about 80% water, although the invention is applicable for any type ofsoft hydrogel contact lens. Representative contact lens materialsinclude, but are not limited to materials known by the following USANand the USAP Dictionary of Drug Names: bufilcon A, etafilcon A,methafilcon A, ocufilcon C, perfilcon A, phemfilcon A, vifilcon A,hilafilcon A, hilafilcon B, balafilcon A, methafilcon B, ocufilcon D,methafilcon A, etafilcon A lidofilcon A or B, and alphafilcon A.

The above materials are merely exemplary, and other materials for use assubstrates that can benefit by being packaged in the aqueous packagingsolution according to the present invention and have been disclosed invarious publications and are being continuously developed for use inophthalmic devices such as contact lenses and other medical devices canalso be used. For example, an ophthalmic device for use herein can be acationic ophthalmic lens such as a cationic contact lens or theophthalmic device can be fluorinated silicone-containing monomers. Suchmonomers have been used in the formation of fluorosilicone hydrogels toreduce the accumulation of deposits on contact lenses made therefrom, asdisclosed in, for example, U.S. Pat. Nos. 4,954,587; 5,010,141 and5,079,319. The use of silicone-containing monomers having certainfluorinated side groups, i.e., —(CF₂)—H, have been found to improvecompatibility between the hydrophilic and silicone-containing monomericunits. See, e.g., U.S. Pat. Nos. 5,321,108 and 5,387,662.

In another embodiment, the present invention is also directed to acontact lens for extended-wear or specialty uses, such as for relativelythick lenses. Extended lenses are lenses capable of being wornovernight, preferably capable of being worn for at least one week, mostpreferably capable of wear for a continuous period of one week to onemonth. By “capable” is meant lenses approved by one or more governmentalregulatory authorities for such consumer use, for example, the U.S. Food& Drug Administration (USFDA) in the U.S. or its equivalent in othercountries.

Extended-wear lenses require relatively high oxygen permeability. Theoxygen-permeability is the rate at which oxygen will pass through amaterial. The oxygen-permeability Dk of a lens material does not dependon lens thickness. Oxygen permeability is measured in terms of barrerswhich have the following units of measurement:

On the other hand, the oxygen transmissibility of a lens, as usedherein, is the rate at which oxygen will pass through a specific lens.Oxygen transmissibility, Dk/t, is conventionally expressed in units ofbarrers/mm, where t is the average thickness of the material (in unitsof mm) over the area being measured. For example, a lens having a Dk ofabout 90 barrers (oxygen-permeability barrers) and a thickness of about90 microns (about 0.090 mm) would have a Dk/t or about 100 barrers/mm(oxygen transmissibility barrers/mm).

Ophthalmic devices such as contact lenses for application of the presentinvention can be manufactured employing various conventional techniques,to yield a shaped article having the desired posterior and anterior lenssurfaces. Spincasting methods are disclosed in U.S. Pat. Nos. 3,408,429and 3,660,545; preferred static casting methods are disclosed in U.S.Pat. Nos. 4,113,224 and 4,197,266. Curing of the monomeric mixture isoften followed by a machining operation in order to provide a contactlens having a desired final configuration. As an example, U.S. Pat. No.4,555,732 discloses a process in which an excess of a monomeric mixtureis cured by spincasting in a mold to form a shaped article having ananterior lens surface and a relatively large thickness. The posteriorsurface of the cured spincast article is subsequently lathe cut toprovide a contact lens having the desired thickness and posterior lenssurface. Further machining operations may follow the lathe cutting ofthe lens surface, for example, edge-finishing operations.

After producing a lens having the desired final shape, it is desirableto remove residual solvent from the lens before edge-finishingoperations. This is because, typically, an organic diluent is includedin the initial monomeric mixture in order to minimize phase separationof polymerized products produced by polymerization of the monomericmixture and to lower the glass transition temperature of the reactingpolymeric mixture, which allows for a more efficient curing process andultimately results in a more uniformly polymerized product. Sufficientuniformity of the initial monomeric mixture and the polymerized productare of particular concern for silicone hydrogels, primarily due to theinclusion of silicone-containing monomers which may tend to separatefrom the hydrophilic comonomer. Suitable organic diluents include, forexample, monohydric alcohols such as C₆-C₁₀ straight-chained aliphaticmonohydric alcohols, e.g., n-hexanol and n-nonanol; diols such asethylene glycol; polyols such as glycerin; ethers such as diethyleneglycol monoethyl ether; ketones such as methyl ethyl ketone; esters suchas methyl enanthate; and hydrocarbons such as toluene. Preferably, theorganic diluent is sufficiently volatile to facilitate its removal froma cured article by evaporation at or near ambient pressure. Generally,the diluent is included at about 5 to about 60 percent by weight of themonomeric mixture, with about 10 to about 50 percent by weight beingespecially preferred.

The cured lens is then subjected to solvent removal, which can beaccomplished by evaporation at or near ambient pressure or under vacuum.An elevated temperature can be employed to shorten the time necessary toevaporate the diluent. The time, temperature and pressure conditions forthe solvent removal step will vary depending on such factors as thevolatility of the diluent and the specific monomeric components, as canbe readily determined by one skilled in the art. According to apreferred embodiment, the temperature employed in the removal step ispreferably at least about 50° C., for example, about 60° C. to about 80°C. A series of heating cycles in a linear oven under inert gas or vacuummay be used to optimize the efficiency of the solvent removal. The curedarticle after the diluent removal step should contain no more thantwenty percent by weight of diluent, preferably no more than about 5percent by weight or less.

Following removal of the organic diluent, the lens can then be subjectedto mold release and optional machining operations. The machining stepincludes, for example, buffing or polishing a lens edge and/or surface.Generally, such machining processes may be performed before or after thearticle is released from a mold part. Preferably, the lens is dryreleased from the mold by employing vacuum tweezers to lift the lensfrom the mold, after which the lens is transferred by means ofmechanical tweezers to a second set of vacuum tweezers and placedagainst a rotating surface to smooth the surface or edges. The lens maythen be turned over in order to machine the other side of the lens

Next, the ophthalmic device will be immersed in an aqueous packagingsolution containing at least an anionic polymer and a non-ionic polyoland stored in a packaging system according to the present invention.Generally, a packaging system for the storage of an ophthalmic deviceaccording to the present invention includes at least a sealed containercontaining one or more unused ophthalmic devices immersed in an aqueouspackaging solution. Preferably, the sealed container is a hermeticallysealed blister-pack, in which a concave well containing a contact lensis covered by a metal or plastic sheet adapted for peeling in order toopen the blister-pack. The sealed container may be any suitablegenerally inert packaging material providing a reasonable degree ofprotection to the lens, preferably a plastic material such aspolyalkylene, PVC, polyamide, and the like.

Any suitable anionic polymer may be employed in accordance with thepresent invention provided that it functions as described herein and hasno substantial detrimental effect on the ophthalmic device such as acontact lens being stored or on the wearer of the lens. The anionicpolymer is preferably ophthalmically acceptable at the concentrationsused. The anionic polymer can include two (2) or more anionic (ornegative) charges, preferably three (3) or more anionic (or negative)charges and most preferably ten (10) or more anionic (or negative)charges. As one skilled in the art will readily appreciate, the anionicpolymer can include multiple charges in the same unit of the polymer orcan include one or more charges on different repeating units in thepolymer. Particularly useful anionic polymers are those which are watersoluble, for example, soluble at the concentrations used in thepresently useful liquid aqueous media, such as a liquid aqueous mediumcontaining the anionic polymer. Particularly useful anionic polymers arethose which are not eliminated during terminal sterilization of thepackaged lenses.

In one embodiment, a class of anionic polymers includes one or morepolymeric materials having multiple anionic charges. In one embodiment,an anionic polymer is an anionic polysaccharide. Representative examplesof suitable anionic polymers for use herein include, but are not limitedto, hyaluronic acid or a derivative thereof and/or salts thereof;carboxymethylcelluloses; carboxymethylhydroxyethylcelluloses;carboxymethylstarch; carboxymethylhydroxyethylstarch; hydrolyzedpolyacrylamides; hydrolyzed polyacrylonitriles; heparin; heparinsulfate, homopolymers and copolymers of one or more acrylic andmethacrylic acids, acrylates and methacrylates; alginic acid or aderivative thereof and/or salts thereof; vinylsulfonic acid or aderivative thereof and/or salts thereof; polymers of amino acids such aspolymers of aspartic acid, glutamic acid and the like or a derivativethereof and/or salts thereof; p-styrenesulfonic acid and the like or aderivative thereof and/or salts thereof; 2-methacryloyloxyethylsulfonicacids or a derivative thereof and/or salts thereof;3-methacryloyloxy-2-hydroxypropylsulfonic acids or a derivative thereofand/or salts thereof; 2-acrylamido-2-methylpropanesulfonic acids or aderivative thereof and/or salts thereof; allylsulfonic acid or aderivative thereof and/or salts thereof; and the like and mixturesthereof. In one embodiment, an anionic polymer is an anionicpolysaccharide. In another embodiment, an anionic polymer includes oneor more of poly(acrylic acid), poly(methacrylic acid), polysaccharides,alginic acid, pectinic acid, carboxymethylcellulose, hyaluronic acid,heparin, heparin sulfate, carboxymethylchitosan, carboxymethylstarch,carboxymethyldextran, chondroitin sulfate, carboxymethylguar, any saltsthereof, and mixtures thereof. The above list is intended forillustrative purposes only and not to limit the scope of the presentinvention. Such polymers are known to those of skill in the art.

In another embodiment, an anionic polymer includes one or more cellulosederivative, anionic polymers derived from acrylic acid (e.g., polymersderived from acrylic acid, acrylates and the like and mixtures thereof),anionic polymers derived from methacrylic acid (e.g., polymers derivedfrom methacrylic acid, methacrylates, and the like and mixturesthereof), anionic polymers derived from alginic acid (e.g., polymersderived from alginic acid, alginates, and the like and mixturesthereof), anionic polymers derived from amino acids (e.g., polymersderived from amino acids, amino acid salts, and the like and mixturesthereof) and mixtures thereof. Particularly useful anionic polymers foruse herein include cellulose polymers such as carboxymethylcelluloses.

The anionic polymer for use herein can have a Mark-Houwink Constantgreater than 0.6, preferably greater than about 1 and more preferablygreater than about 1.6. In one embodiment, the anionic polymer can havea Mark-Houwink Constant between about 1 to about 1.4. The Mark-Houwinkconstant (α) is calculated using the technique disclosed in Introductionto Physical Polymer Science, Third Edition, L. H. Sperling,Wiley-Interscience, A John Wiley & Sons, Inc., Publication, New York,2001. Interpretation of the Mark-Houwink constant for CMC is illustratedbelow in Table 1:

TABLE 1 Values of the Mark-Houwink Constants (α) Mark-Houwink Constants(α) Interpretation 0   Spheres 0.5–0.8 Random coils 1.0 Stiff coils 2.0Rods

A Mark-Houwink Constant of zero is indicative of a spherical polymericstructure. A Mark-Houwink Constant between 0.5 and 0.8 indicates aphysical configuration described as random coils. A Mark-HouwinkConstant above 0.8 indicates a structure that is more ordered thanrandom approaching a stiff coil. A Mark-Houwink Constant of about 1.0 isa stiff coil and a Mark-Houwink Constant of 2.0 represents a rod-likestructure.

In one embodiment, the carboxy-containing polymer is an anioniccarboxy-containing polysaccharide. Suitable polysaccharides of thepresent invention include carboxy-containing polysaccharides such as,for example, a carboxy-containing cellulose, hyaluronate, chondroitinsulfate, algin, pectin and xanthan. The anionic polymer could also bederived from carboxy-containing vinyl polymers, such as carbomers,poly(acrylic acid and poly(methacrylic acid), and derivatives thereof,or from anionic polypeptides, such as poly(glutamic acid) andpoly(aspartic acid), and derivatives thereof.

In one embodiment, the average molecular weight of an anioniccarboxy-containing polymer is a minimum of about 90 kDa and a maximum ofabout 700 kDa. Generally, the average molecular weight of the anioniccarboxy-containing polymer is a minimum of about 150 kDa, preferably aminimum of about 200 kDa, and more preferably a minimum of about 250.The average molecular weight of the anionic carboxy-containing polymeris a maximum of about 650 kDa, preferably a maximum of about 600 kDa,more preferably a maximum of about 550 kDa and most preferably a maximumof about 500 kDa.

The amount of the anionic polymer present in the aqueous packagingsolution is that amount effective to improve the surface properties ofthe ophthalmic device when combined with a non-ionic polyol. Preferably,the anionic polymer is present in the packaging solution of theinvention in an amount of at least about 0.01% w/v. The specific amountof such anionic polymers used can vary widely depending on a number offactors, for example, the specific anionic polymer and non-ionic polyolbeing employed. Generally, the concentration of the anionic polymer isfrom about 0.01 to about 10% w/w and preferably from about 0.5 to about1.5% w/w.

It is likewise preferable that the anionic polymer have a degree ofsubstitution value that is a minimum of about 0.5 and a maximum of about1.5. Preferably, the anionic polymer can have a degree of substitutionvalue that is a minimum of about 0.9 to a maximum of about 1.1.

In one embodiment, the non-ionic polyol for use herein can be anon-ionic polyol containing 2 to about 12 carbon atoms and preferably 2to 4 carbon atoms and from 2 to 6 hydroxyl groups. Representativeexamples of such non-ionic polyols include glycerin, ethylene glycol,poly(ethylene glycol), propylene glycol, sorbitol, mannitol,monosaccharides, disaccharides, and neutral oligo-polysaccharides, suchas from methylcellulose, hydroxypropylmethylcellulose, guar,hydroxypropylguar, and oligomers of poly(vinyl alcohol) and derivativesthereof, and the like and mixtures thereof. In one embodiment, anon-ionic polyol can be glycerin, ethylene glycol, propylene glycol,sorbitol, mannitol, monosaccharides and mixtures thereof. In anotherembodiment, the non-ionic polyol can be disaccharides, oligosaccharides,poly(ethylene glycol) and mixtures thereof. In a preferred embodiment,the non-ionic polyol is glycerin.

The amount of non-ionic polyol present in the aqueous packaging solutionwill generally be an amount sufficient to increase the Mark-HouwinkConstant of the anionic polymer in the solution such that a relativelymore uniform coating can be formed on the surface of the device whenpackaged in a solution according to the present invention. In general,the concentration of the non-ionic polyol in the solution willordinarily range from about 0.01 to about 10% w/w and preferably fromabout 0.5 to about 3% w/w.

The aqueous packaging solutions according to the present invention arephysiologically compatible. Specifically, the solution must be“ophthalmically safe” for use with a lens such as a contact lens,meaning that a contact lens treated with the solution is generallysuitable and safe for direct placement on the eye without rinsing, thatis, the solution is safe and comfortable for daily contact with the eyevia a contact lens that has been wetted with the solution. Anophthalmically safe solution has a tonicity and pH that is compatiblewith the eye and includes materials, and amounts thereof, that arenon-cytotoxic according to ISO standards and U.S. Food & DrugAdministration (FDA) regulations. The solution should be sterile in thatthe absence of microbial contaminants in the product prior to releasemust be statistically demonstrated to the degree necessary for suchproducts. The liquid media useful in the present invention are selectedto have no substantial detrimental effect on the lens being treated orcared for and to allow or even facilitate the present lens treatment ortreatments. The liquid media are preferably aqueous-based. Aparticularly useful aqueous liquid medium is that derived from saline,for example, a conventional saline solution or a conventional bufferedsaline solution.

The pH of the present aqueous packaging solutions should be maintainedwithin the range of about 6.0 to about 9, and preferably about 6.5 toabout 7.8. Suitable buffers may be added, such as boric acid, sodiumborate, potassium citrate, citric acid, sodium bicarbonate,tris(hydroxymethyl)aminomethane, and various mixed phosphate buffers,e.g., combinations of Na₂HPO₄, NaH₂PO₄ and KH₂PO₄, and the like andmixtures thereof. Generally, buffers will be used in amounts rangingfrom about 0.05 to about 2.5% by weight, and preferably from about 0.1to about 1.5% by weight of the solution.

Typically, the aqueous packaging solutions of the present invention arealso adjusted with tonicity agents, to approximate the osmotic pressureof normal lacrimal fluids. The solutions are made substantially isotonicwith physiological saline used alone or in combination, otherwise ifsimply blended with sterile water and made hypotonic or made hypertonicthe lenses will lose their desirable optical parameters.Correspondingly, excess saline may result in the formation of ahypertonic solution which will cause stinging and eye irritation.

Examples of suitable tonicity adjusting agents include, but are notlimited to, sodium and potassium chloride, dextrose, glycerin, calciumand magnesium chloride and the like and mixtures thereof. These agentsare typically used individually in amounts ranging from about 0.01 toabout 2.5% w/v and preferably from about 0.2 to about 1.5% w/v.Generally, a 0.9% solution of sodium chloride is equivalent inosmolality to a 3 percent of glycerol solution or a 5 percent solutionof monosaccharide, so the amount of a specific agent will vary dependingon the agent used. Preferably, the tonicity agent will be employed in anamount to provide a final osmotic value of at least about 200 mOsm/kg,preferably from about 200 to about 400 mOsm/kg, and more preferably fromabout 250 to about 350 mOsm/kg.

If desired, one or more additional components can be included in theaqueous packaging solutions. Such additional component or components arechosen to impart or provide at least one beneficial or desired propertyto the packaging solution. Such additional components may be selectedfrom components which are conventionally used in one or more ophthalmicdevice care compositions. Examples of such additional components includecleaning agents, wetting agents, nutrient agents, sequestering agents,viscosity builders, contact lens conditioning agents, antioxidants, andthe like and mixtures thereof. These additional components may each beincluded in the packaging solutions in an amount effective to impart orprovide the beneficial or desired property to the packaging solutions.For example, such additional components may be included in the packagingsolutions in amounts similar to the amounts of such components used inother, e.g., conventional, contact lens care products.

Useful sequestering agents include, but are not limited to, disodiumethylenediaminetetraacetic acid (EDTA), alkali metal hexametaphosphate,citric acid, sodium citrate and the like and mixtures thereof.

Useful viscosity builders include, but are not limited to,hydroxyethylcellulose, methylcellulose, hydroxypropylmethylcellulose,poly(N-vinylpyrrolidone), guar, hydroxyethylguar, hydroxypropylguar,poly(vinyl alcohol) and the like and mixtures thereof.

Useful antioxidants include, but are not limited to, sodiummetabisulfite, sodium thiosulfate, N-acetylcysteine, butylatedhydroxyanisole, butylated hydroxytoluene and the like and mixturesthereof.

The method of packaging and storing an ophthalmic device such as acontact lens according to the present invention includes at leastpackaging an ophthalmic device immersed in the aqueous packagingsolution described above. The method may include immersing theophthalmic device in an aqueous solution prior to delivery to thecustomer/wearer, directly following manufacture of the device.Alternately, the packaging and storing in the solution of the presentinvention may occur at an intermediate point before delivery to theultimate customer (wearer) but following manufacture and transportationof the lens in a dry state, wherein the dry lens is hydrated byimmersing the lens in the aqueous packaging solution. Consequently, apackage for delivery to a customer may include a sealed containercontaining one or more unused contact lenses immersed in an aqueouspackaging solution according to the present invention.

In one embodiment, the steps leading to the present ophthalmic lenspackaging system includes (1) molding an ophthalmic lens in a moldcomprising a posterior and anterior mold portion, (2) removing the lensfrom the mold and hydrating the lens, (3) introducing the aqueouspackaging solution with the anionic polymer and non-ionic polyol intothe container with the lens supported therein, and (4) sealing thecontainer. Preferably, the method also includes the step of sterilizingthe contents of the container. Sterilization may take place prior to, ormost conveniently after, sealing of the container and may be effected byany suitable method known in the art, e.g., by autoclaving of the sealedcontainer and its contents at temperatures of about 120° C. or higher.

The following examples are provided to enable one skilled in the art topractice the invention and are merely illustrative of the invention. Theexamples should not be read as limiting the scope of the invention asdefined in the claims.

EXAMPLE 1

A clean hilafilcon A lens, which is a copolymer composed mainly of HEMAand NVP, was soaked in a lens packaging solution within the scope of thepresent invention overnight and autoclaved for 30 minutes at 121° C. Theingredients and amounts of the solution are set forth in Table 2. Thecarboxymethylcellulose was a medium viscosity (MV) grade (viscosity nogreater than 30 cp). The XPS results for the lens are set forth below inTable 4.

TABLE 2 Ingredients % w/w Sodium borate 0.215 Boric acid 1.000Ethylenediaminetetraacetic 0.050 acid (EDTA) Carboxymethylcellulose1.000 (MV) Glycerin 1.000 pH = 7.16 Osmolality = 347 mOsm/kg

COMPARATIVE EXAMPLE A

A clean hilafilcon A lens as used in Example 1 was soaked in a lenspackaging solution outside the scope of the invention overnight andautoclaved for 30 minutes at 121° C. The ingredients and amounts of thesolution are set forth in Table 3. The XPS results for the lens are setforth below in Table 4.

TABLE 3 Ingredients % w/w Sodium borate 0.215 Boric acid 1.000 EDTA0.050 Carboxymethylcellulose 1.000 (MV) pH = 7.49 Osmolality = 237mOsm/kg

Testing

Sample specimens prepared in Example 1 and Comparative Example A wereanalyzed for its atomic concentration by XPS and compared to a cleanhilafilcon A lens rich in HEMA and NVP content which was not soaked in apackaging solution and autoclaved. The X-ray Photoelectron Spectrometer(XPS) utilized in this study was a Physical Electronics [PHI] Model5600. This instrument utilized an aluminum anode operated at 300 watts,15 kV and 27 milliamps. The excitation source was monochromatizedutilizing a torodial lens system. The 7 mm filament was utilized for thepolymer analysis due to the reduced sample damage and ease ofphotoionization neutralization. The base pressure of this instrument was2.0×10⁻¹⁰ torr while the pressure during operation was 1.0×10⁻⁹ torr.This instrument made use of a hemispherical energy analyzer. Thepractical measure of sampling depth for this instrument at a samplingangle of 45° and with respect to carbon was approximately 74 angstroms.All elements were charge corrected to the CH_(x) peak of carbon to abinding energy of 285.0 electron volts (eV).

Each of the specimens was analyzed utilizing a low resolution surveyspectra [0-1100 eV] to identify the elements present on the samplesurface. The high resolution spectra were performed on those elementsdetected from the low resolution scans. The elemental composition wasdetermined from the high resolution spectra. The atomic composition wascalculated from the areas under the photoelectron peaks aftersensitizing those areas with the instrumental transmission function andatomic cross sections for the orbital of interest. Since XPS does notdetect the presence of hydrogen or helium, these elements will not beincluded in any calculation of atomic percentages. It is also noted thatatomic percentages may vary if a different instrument design, i.e.,transmission function, is utilized, so that for purposes of exactreproducibility the atomic percentage numbers in the application referto the specified instrument design, as will be understood by the skilledartisan.

The low resolution XPS survey spectra taken at a takeoff angle of 45°for the untreated lens' surfaces contained peaks for carbon, nitrogen,oxygen, boron and sodium. The analysis of the lens' material begins withthe examination of the unmodified matrix (control). Table 4 belowcontains the XPS data for the samples. This data reflects the atomiccomposition over the top 74 angstroms (relative to carbon 1 selectrons). The percentages reflect all elements except hydrogen andhelium.

TABLE 4 Atomic Concentration Carbon Nitrogen Oxygen Boron Sodium CleanedProduct 74.6 4.1 21.3 0.0 0.0 Comp. Ex. A 72.9 3.7 22.3 1.1 0.0 Ex. 170.2 1.8 25.7 1.4 0.9

As can be seen from Table 4, the amount of nitrogen in the lens soakedin a packaging solution containing both an anionic polymer and anon-ionic polyol of the present invention is substantially reduced whencompared to a lens soaked in a packaging solution containing only ananionic polymer. The substantial reduction in the amount of nitrogenpresent on the lens indicates that the surface of the lens has beencovered with the components of the packaging solution, thereby providinga more uniform coating thereon.

It will be understood that various modifications may be made to theembodiments disclosed herein. Therefore the above description should notbe construed as limiting, but merely as exemplifications of preferredembodiments. For example, the functions described above and implementedas the best mode for operating the present invention are forillustration purposes only. Other arrangements and methods may beimplemented by those skilled in the art without departing from the scopeand spirit of this invention. Moreover, those skilled in the art willenvision other modifications within the scope and spirit of the featuresand advantages appended hereto.

1. A method of preparing a package comprising a storable, sterileophthalmic device, the method comprising: (a) immersing an ophthalmicdevice in an aqueous packaging solution comprising an anionic polymerand a non-ionic polyol, wherein the aqueous packaging solution has anosmolality of at least about 200 mOsm/kg and a pH in the range of about6 to about 9; (b) packaging the solution and the device in a mannerpreventing contamination of the device by microorganisms; and (c)sterilizing the packaged solution and device.
 2. The method of claim 1,wherein the ophthalmic device is a contact lens.
 3. The method of claim1, wherein the ophthalmic device comprises a polymerization product of amonomeric mixture comprising one or more silicone-containing monomers.4. The method of claim 1, wherein the anionic polymer possesses aMark-Houwink Constant of greater than 0.6.
 5. The method of claim 1,wherein the anionic polymer possesses a Mark-Houwink Constant of greaterthan about
 1. 6. The method of claim 1, wherein the anionic polymerpossesses a Mark-Houwink Constant of greater than about 1.6.
 7. Themethod of claim 1, wherein the anionic polymer in the aqueous packagingsolution is a carboxy-containing polysaccharide.
 8. The method of claim7, wherein the carboxy-containing polysaccharide is selected from thegroup consisting of a carboxy-containing cellulose, hyaluronate,chondroitin sulfate, guar, alginate, pectin, xanthan and mixturesthereof.
 9. The method of claim 7, wherein the carboxy-containingpolysaccharide is a carboxymethylcellulose.
 10. The method of claim 1,wherein the anionic polymer in the aqueous packaging solution is acarboxy-containing vinyl polymer.
 11. The method of claim 10, where thecarboxy-containing vinyl polymer is selected from the group consistingof a carbomer, polymer of acrylic acid and/or methacrylic acid andmixtures thereof.
 12. The method of claim 1, wherein the anionic polymerin the aqueous packaging solution is an anionic polypeptide.
 13. Themethod of claim 12, wherein the anionic polypeptide is selected from thegroup consisting of a poly(glutamic acid), poly(aspartic acid) andmixtures thereof.
 14. The method of claim 1, wherein the anionic polymerhas a degree of substitution value of about 0.5 to about 1.5.
 15. Themethod of claim 1, wherein the concentration of the anionic polymer inthe aqueous packaging solution is about 0.01 to about 10% w/w.
 16. Themethod of claim 1, wherein the non-ionic polyol is selected from thegroup consisting of glycerin, ethylene glycol, poly(ethylene glycol),propylene glycol, monosaccarides, disaccharides, oligopolysaccharides orpolysaccharides and mixtures thereof.
 17. The method of claim 1, whereinthe anionic polymer is a carboxymethylcellulose and the non-ionic polyolis glycerin.
 18. The method of claim 1, wherein the solution furthercomprises a buffering agent.
 19. The method of claim 1, wherein theaqueous packaging solution coats the ophthalmic device more uniformlythan that of a similar aqueous packaging solution in which the non-ionicpolyol is not present in the aqueous packaging solution.
 20. The methodof claim 1, further comprising hermetically sealing the ophthalmicdevice and the aqueous packaging solution in the package.
 21. The methodof claim 20, wherein heat sterilization is performed subsequent tosealing of the package.
 22. The method of claim 1, wherein the aqueouspackaging solution does not contain an effective disinfecting amount ofa disinfecting agent.
 23. The method of claim 1, wherein the aqueouspackaging solution does not contain a germicide compound.
 24. Apackaging system for the storage of an ophthalmic device comprising asealed container containing one or more unused ophthalmic devicesimmersed in an aqueous packaging solution comprising an anionic polymerand a non-ionic polyol, wherein the aqueous packaging solution has anosmolality of at least about 200 mOsm/kg, a pH of about 6 to about 9 andis heat sterilized.
 25. The packaging system of claim 24, wherein theophthalmic device is a contact lens.
 26. The packaging system of claim24, wherein the ophthalmic device comprises a polymerization product ofa monomeric mixture comprising one or more silicone-containing monomers.27. The packaging system of claim 24, wherein the anionic polymerpossesses a Mark-Houwink Constant of greater than 0.6.
 28. The packagingsystem of claim 24, wherein the anionic polymer possesses a Mark-HouwinkConstant of greater than about
 1. 29. The packaging system of claim 24,wherein the anionic polymer possesses a Mark-Houwink Constant of greaterthan about 1.6.
 30. The packaging system of claim 24, wherein theanionic polymer in the aqueous packaging solution is acarboxy-containing polysaccharide.
 31. The packaging system of claim 30,wherein the carboxy-containing polysaccharide is selected from the groupconsisting of a carboxy-containing cellulose, hyaluronate, chondroitinsulfate, carboxy-containing guar, alginate, pectin, xanthan and mixturesthereof.
 32. The packaging system of claim 30, wherein thecarboxy-containing polysaccharide is a carboxymethylcellulose.
 33. Thepackaging system of claim 24, wherein the anionic polymer has a degreeof substitution value of about 0.5 to about 1.5.
 34. The packagingsystem of claim 24, wherein the concentration of the anionic polymer inthe aqueous packaging solution is about 0.01 to about 10% w/w.
 35. Thepackaging system of claim 24, wherein the non-ionic polyol is selectedfrom the group consisting of glycerin, ethylene glycol, poly(ethyleneglycol), propylene glycol, monosaccarides, disaccharides,oligopolysaccharides or polysaccharides and mixtures thereof.
 36. Thepackaging system of claim 24, wherein the anionic polymer is acarboxymethylcellulose and the non-ionic polyol is glycerin.
 37. Thepackaging system of claim 24, wherein the aqueous packaging solutionfurther comprises a buffering agent.
 38. The packaging system of claim24, wherein the aqueous packaging solution coats the ophthalmic devicemore uniformly than that of a similar aqueous packaging solution inwhich the non-ionic polyol is not present in the solution.
 39. Thepackaging system of claim 24, wherein package is heat sterilizedsubsequent to sealing of the package.
 40. The packaging system of claim24, wherein the solution does not contain an effective disinfectingamount of a disinfecting agent.
 41. The packaging system of claim 24,wherein the aqueous packaging solution does not contain a germicidecompound.